TY - JOUR
T1 - NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer
AU - Leung, Elaine
AU - Ennis, Darren
AU - Kennedy, Philippa
AU - Hansell, Christopher
AU - Dowson, Suzanne
AU - Farquharson, Malcolm
AU - Spiliopoulou, Pavlina
AU - Nautiyal, Jaya
AU - McNamara, Sophie
AU - Carlin, Leo M.
AU - Fisher, Kerry
AU - Davis, Daniel M
AU - Graham, Gerard J
AU - McNeish, Iain A
PY - 2020/2/10
Y1 - 2020/2/10
N2 - Oncolytic viruses (OV) can trigger profound innate and adaptive immune responses, which have the potential both to potentiate and reduce the activity of OV. Natural Killer (NK) cells can mediate potent anti-viral and anti-tumoural responses, but there are no data on the role of NK cells in oncolytic adenovirus activity. Here, we have used two different oncolytic adenoviruses – the Ad5 E1A CR2-deletion mutant dl922-947 (group C) and the chimeric Ad3/Ad11p mutant enadenotucirev (group B) – to investigate the effect of NK cells on overall anti-cancer efficacy in ovarian cancer. Because human adenoviruses do not replicate in murine cells, we utilised primary human NK cells from peripheral blood and ovarian cancer ascites. Our results show that dl922-947 and enadenotucirev do not infect NK cells, but induce contact-dependent activation and anticancer cytotoxicity against adenovirus-infected ovarian cancer cells. Moreover, manipulation of NK receptors DNAM-1 and TIGIT significantly influences NK cytotoxicity against adenovirus-infected cells. Together, these results indicate that NK cells act to increase the activity of oncolytic adenovirus in ovarian cancer and suggest that strategies to augment NK activity further via the blockade of inhibitory NK receptor TIGIT could enhance therapeutic potential of OV.
AB - Oncolytic viruses (OV) can trigger profound innate and adaptive immune responses, which have the potential both to potentiate and reduce the activity of OV. Natural Killer (NK) cells can mediate potent anti-viral and anti-tumoural responses, but there are no data on the role of NK cells in oncolytic adenovirus activity. Here, we have used two different oncolytic adenoviruses – the Ad5 E1A CR2-deletion mutant dl922-947 (group C) and the chimeric Ad3/Ad11p mutant enadenotucirev (group B) – to investigate the effect of NK cells on overall anti-cancer efficacy in ovarian cancer. Because human adenoviruses do not replicate in murine cells, we utilised primary human NK cells from peripheral blood and ovarian cancer ascites. Our results show that dl922-947 and enadenotucirev do not infect NK cells, but induce contact-dependent activation and anticancer cytotoxicity against adenovirus-infected ovarian cancer cells. Moreover, manipulation of NK receptors DNAM-1 and TIGIT significantly influences NK cytotoxicity against adenovirus-infected cells. Together, these results indicate that NK cells act to increase the activity of oncolytic adenovirus in ovarian cancer and suggest that strategies to augment NK activity further via the blockade of inhibitory NK receptor TIGIT could enhance therapeutic potential of OV.
M3 - Article
SN - 2372-7705
JO - Molecular therapy oncolytics
JF - Molecular therapy oncolytics
ER -
